The 202nd meeting of the National Advisory Allergy and Infectious Diseases Council (NAAIDC) convened virtually at 10:30 a.m. on Monday, September 12, 2022. Dr. Anthony S. Fauci, Director, National Institute of Allergy and Infectious Diseases (NIAID) presided as chair.
In accordance with the provisions of Public Law 92-463, the meeting was open to the public from 10:30 a.m. to 11:44 a.m. and from 1:00 p.m. to 4:00 p.m. The meeting was closed to the public from 8:30 a.m. to 10:30 a.m. and from 11:45 a.m. to 12:00 noon for review and consideration of individual grant applications. Notice of the meeting was published in the Federal Register.
|Ex Officio Members Present||
|Ad Hoc Members Present||
|NIAID Senior Staff Present||
Table of Contents
I. Review of Grant Applications
II. Remarks of the Director, NIAID—Anthony S. Fauci, M.D.
III. Guest Speaker—Steven M. Holland, M.D., Director, Division of Intramural Research, NIAID
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., Director, DAIT
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., Director, DMID
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., Director, DAIDS
The National Advisory Allergy and Infectious Diseases Council convened in closed session to consider applications in allergy and immunology, microbiology and infectious diseases, and AIDS.
Funding Actions: The Council reviewed 4,420 research and training applications with primary assignment to NIAID for a requested amount of $1,409,848,126 in first-year direct costs and recommended approval of 1,621 applications with $511,610,169 in first-year direct costs.
Dr. Fauci opened the Council session by welcoming visitors to the meeting. He also introduced two ad hoc members: Dr. David Artis, the Michael Kors Professor of Immunology in the Department of Medicine at Weill Cornell Medical College, and Dr. De’Broski Herbert, the Presidential Professor of Immunology at the University of Pennsylvania, and Professor of Pathobiology in the UPenn School of Veterinary Medicine.
Council member Dr. Linda Bockenstedt was unable to attend the meeting.
Consideration of Minutes of Previous Meeting
Council considered the minutes of the June 6, 2022 meeting and concepts that had been presented and approved them as written.
Staff and Organizational Changes
Dr. Fauci announced appointments and transitions that have taken place since the last Council meeting.
President Biden has nominated Dr. Arati Prabhakar to serve as the Director of the White House Office of Science and Technology Policy.
On August 2, the Biden Administration announced the appointments of Robert Fenton, Jr., as the White House National Monkeypox Response Coordinator, and Dr. Demetre Daskalakis, Director of the CDC Division of HIV Prevention, as Deputy Coordinator.
In July, FDA Commissioner Dr. Robert Califf announced appointments to two FDA senior leadership positions. Dr. Namandjé Bumpus is the new FDA Chief Scientist, and Dr. Hilary Marston is now the FDA Chief Medical Officer.
President Biden has selected Dr. Monica Bertagnolli as the next Director and the first woman to lead the National Cancer Institute.
In June, Acting NIH Director Dr. Larry Tabak announced the selection of Kevin Williams as Director of the NIH Office of Equity, Diversity, and Inclusion.
Dr. Fauci provided an update on NIAID activities related to diversity, equity, inclusion, and accessibility (DEIA). NIAID has established an internal DEIA Council that is advising Institute leadership on many of the activities. Also, NIAID will be issuing a request for information to allow the extramural community to share thoughts and suggestions on how to enhance DEIA across NIAID activities.
In the Division of Extramural Activities, Aileene Lewis was named Chief of the Microbiology and Infectious Diseases Contracts—Branch B in the Office of Acquisitions.
The Technology Transfer and Intellectual Property Office (TTIPO) selected two new branch chiefs. Dr. Cosimo Fuda is Chief of TTIPO Branch A, and Dr. Sabarni Chatterjee is Chief of TTIPO Branch B.
Stephanie Hixson is the new Director of NIAID’s Office of Workplace Solutions.
Meetings and Events
Dr. Fauci reported on virtual and in-persons meetings that he attended with international delegations and health officials, including the Chief Medical Officer for England, the WHO Regional Director for Europe, a delegation of senior United Arab Emirates health officials, and the German Minister of Health.
On July 8, NIAID entered into a research collaboration agreement with Afrigen Biologics and Vaccines, a biotechnology company based in Cape Town, South Africa. Afrigen serves as the mRNA vaccine center of excellence and training, part of an effort led by WHO to build capacity in low- and middle-income countries to make mRNA vaccines. The collaboration will enable scientists at NIAID’s Vaccine Research Center and Afrigen to share knowledge, expertise, and data on mRNA vaccine production processes to support their respective missions.
Since the President released his fiscal year (FY) 2023 budget in March, the House and Senate both released draft budgets for NIH. The overall proposed increase for NIH is 5.5 percent under the House bill and 6.6 percent under the Senate bill.
Dr. Fauci noted that NIH expects to start FY 2023 under a continuing resolution.
He presented NIAID’s interim FY 2023 financial management plan. Taking a conservative funding approach, our interim R01 paylines are the 10th percentile for established principal investigators (PIs) and the 14th percentile for new PIs. NIAID does not plan to make programmatic adjustments to competing, unsolicited awards, noncompeting grants, and research and development awards. Competing research initiatives have been cut by up to 20 percent to sustain new investigator-initiated awards. Our estimated success rates for research project grants will be 18 to 22 percent.
Dr. Fauci summarized proposed budget earmark allocations that include increases for antimicrobial resistance research and developing universal influenza vaccines.
He also provided an update on the funding NIAID and NIH received to respond to the COVID-19 pandemic and coronaviruses, as well as NIAID’s investment of $0.7 billion through the American Rescue Plan Act to implement the Antiviral Program for Pandemics, which includes about $600 million awarded to nine Antiviral Drug Discovery Centers.
On September 2, the Biden Administration announced its FY 2023 supplemental budget request of $4.5 billion to address the current monkeypox outbreak. The request includes almost $200 million for HHS for high-priority research and development, such as evaluating vaccine effectiveness in special populations and developing rapid diagnostic tests.
On June 16, Dr. Fauci testified at a Senate Health, Education, Labor, and Pensions Committee hearing to provide an update on the ongoing federal response to COVID-19. He acknowledged NIAID staff who participated in many Congressional briefings on his behalf.
Dr. Fauci paid tribute to Congressman John Porter who passed away in June 2022. Congressman Porter provided strong and sustained support for NIH, and he will be greatly missed by the NIH community.
Other Information Items
Dr. Fauci began with an HIV/AIDS update, noting that the 24th International AIDS Conference was held in Montreal, Canada, from July 27 to August 2, 2022, as a hybrid meeting. The meeting theme was to re-engage and follow the science. He highlighted new and interesting research that was presented at the meeting, as well as other promising HIV/AIDS research accomplishments.
Dr. Fauci continued with an update on the monkeypox outbreak, including the number of confirmed cases worldwide, countries with the most cases, available countermeasures, FDA emergency use authorization of the JYNNEOS vaccine, and a list of NIAID’s monkeypox clinical trials.
Next, he gave an update on COVID-19, noting recent papers published in Cell and Science showing strong evidence for the natural occurrence and evolution of the COVID-19 outbreak from the Wuhan Market in central China. Dr. Fauci then provided recent statistics on the number of COVID-19 cases and deaths globally and in the United States, and information about current variants, therapeutics available for non-hospitalized patients with COVID-19, and vaccines currently available.
Dr. Fauci mentioned the need for next generation coronavirus vaccines, either pan-coronavirus vaccines or mucosal vaccines, and summarized ongoing research in these areas.
He concluded with updates on research related to monoclonal antibodies to prevent malaria; the prototype pathogen approach for vaccine and monoclonal antibody development, which is a critical component of the broader NIAID plan for pandemic preparedness; and hepatitis B.
Dr. Fauci acknowledged the contributions of five retiring Council members—Elling Eidbo and Drs. Ritu Agarwal, Amita Gupta, Gwendalyn Randolph, and Anuradha Ray—and thanked them for their service.
Dr. Fauci announced that after 38 years presiding over NIAID Council meetings, this was the last Council Meeting that he would address as NIAID Director. He thanked all the current and past Council members who have served over the years.
Dr. Holland began with a brief explanation of how the Division of Intramural Research (DIR) evaluates its research – the Board of Scientific Counselors reviews every lab, every principal investigator (PI) at least every 4 years. Reviews are done in June and December. He shared a snapshot of the number of PIs in DIR broken down by tenured and tenure track PIs.
Dr. Holland explained that NIAID’s intramural programs are in Bethesda and at the Rocky Mountain Laboratories in Montana, along with sites around the world.
He reviewed DIR’s priorities, which are:
- Transformative medicine and biomedical research
- Bench-to-bedside research taking advantage of NIH’s Clinical Center, as well as domestic and international clinical sites
- Responding to public health threats, including drug-resistant microbes, emerging viruses, and needed vaccines
- Partnering to advance vaccines, therapeutics, and diagnostics for infectious and immunologic diseases
Dr. Holland gave an overview of DIR’s activities over the last year, which included over 800 publications and about 200 active clinical studies. Sixty percent of DIR’s PIs have taken on and developed COVID projects leading to 451 publications.
One new area of focus for DIR was the creation of a SARS-CoV-2 Virology Core to support COVID-19 bench and animal work by any NIH intramural investigators from laboratories that do not have biosafety level 3 capacity. The program has been successful as a starter paradigm for pandemic preparedness. Dr. Holland also mentioned that monkeypox has become an important research area, with DIR studying the viral evolution, diagnostics, therapeutics, transmission, and environmental stability.
Dr. Holland outlined DIR staff changes that have occurred over the last year, including new branch chiefs and deputy lab chiefs, a new tenured investigator, new tenure-track investigators, staff departures, and upcoming retirements. He also noted lab closings and searches for new lab chiefs and tenure and tenure-track positions.
He highlighted some of DIR’s scientific research on COVID-19, Crimean-Congo hemorrhagic fever, fungal infections, and intestinal host commensal homeostasis. Dr. Holland concluded by summarizing future priorities, such as recruiting talented diverse investigators; continuing to support outstanding basic science; fostering bench-to-bedside approaches; making Clinical Center resources available to all labs; promoting pathophysiology, innovative strategies, vaccine targets, diagnostics, and therapeutics; and encouraging extramural and international collaborations.
IV. Report of the Allergy, Immunology, and Transplantation Subcommittee–Daniel Rotrosen, M.D., Director, DAIT
Dr. Rotrosen welcomed the subcommittee members to the 202nd meeting of the National Advisory Allergy and Infectious Diseases Subcommittee meeting.
Dr. Rotrosen presented the following scientific and Division activities:
Staff and Organizational Changes
Maggie Morris Fears, Ph.D., Dr. Morris Fears joined the Autoimmunity and Mucosal Immunology Branch as a Program Officer July 2022. Dr. Morris Fears joined the NIH in 2019, where she served as a Scientific Review Officer in NIAID’s Scientific Review Program (SRP), and also served in two acting roles, as Deputy Chief of the Immunology Review Branch and as the acting Knowledge Management Coordinator. She also was involved in SRP’s diversity and inclusion initiatives. Prior to that, Dr. Morris Fears was an Associate Professor in the Department of Internal Medicine at Eastern Virginia Medical School (EVMS), where she also served as the Director of Biomedical Sciences Graduate Programs. While at EVMS, she researched the role of innate immunity and inflammatory processes in the pathogenesis of Type 1 Diabetes. Dr. Morris Fears earned her Ph.D. in immunology from the University of Texas Southwestern Medical Center at Dallas and received her Bachelor of Science degree in biology from the University of Michigan.
Selected Funding Opportunities
Allergy, Asthma, and Airway Biology Branch
Food Protein-Induced Enterocolitis Syndrome (FPIES) Workshop. On June 22, 2022, a virtual workshop was held by the NIAID/DAIT/AAABB. The meeting brought together patient advocacy representatives, clinicians, and researchers with expertise in FPIES, as well as representatives from the broader immunologic community to present what is known about the disease and explore the most pressing issues for patients with this disease. The objective of this workshop was for NIAID to obtain expert input in identifying research needs in the pathophysiology, diagnosis, and management of FPIES. The presenters and NIAID staff are collaborating on a workshop summary for publication in the near future.
Basic Immunology Branch
Systems Immunology Program. On May 31, 2022, NIAID virtually held the last annual programmatic meeting of the DAIT Systems Immunology U19 Cooperative Agreement program. Investigators from Harvard University, University of North Carolina at Chapel Hill, and Scripps Research Institute reviewed the history of the program; discussed the major scientific discoveries; and presented animal models, reagents, cutting-edge technologies, and analytical tools resulting from the program during the past 20 years. The three U19 groups also reported current progress on their projects and recent updates on COVID-19 research during the year. The meeting provided a venue for investigators to review their past accomplishments, exchange ideas, foster collaborations, and leverage resources and expertise to advance the field.
Human Immunology Project Consortium (HIPC). On June 9, 2022, NIAID held a kick-off Zoom meeting for the FY 2022 renewal of the HIPC program. This trans-NIAID program, led by DAIT, consists of a coordinating center and eight multiproject cooperative agreements (U19s), which will collect detailed clinical data and conduct immune profiling on diverse human cohorts at steady state and in response to pathogenic infections or vaccines. The HIPC Coordinating Center will foster collaborative activities across HIPC, including managing an infrastructure and opportunity fund, further develop and implement clinical and immunologic data standards, and maintain and expand a human immunology knowledgebase and analysis portal, ImmuneSpace (https://www.immunespace.org).
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) Collaborative Research Centers. On June 13 and 14, 2022, the annual meeting of the NIH ME/CFS Collaborative Research Centers program, by a multi-Institute and Center (IC) supported consortium, was held in Bethesda, Maryland. The four centers in the program, one of which is funded by NIAID, reported significant progress made towards a better understanding of the pathogenesis of ME/CFS including advances in understanding the energy metabolism, lipid metabolites, and biomarkers found in patients when compared to healthy controls. This meeting showed the most detailed metabolic differences yet seen between groups. This network will renew in 2023 after submission and review of progress by NIH peer review.
T Cell Technologies: Assays, Innovations, Challenges, and Opportunities Workshop. On June 15 and 16, 2022, NIAID/DAIT held a virtual workshop focusing on exploring the challenges and opportunities for improved T cell immune diagnostics to identify specific effector functions and T cell lineages associated with clinical and experimental outcomes. Speakers reviewed the best current evaluation methods for T cell activation and function, discussed evolving assays through the adaption of new technologies, and addressed T cell functional analyses in clinical settings. The challenges in detecting and functional assessment of T cells and future directions also were discussed.
Characterizing and Improving Humanized Immune System Mouse Models. On July 8, 2022, the annual meeting of the contract program to characterize and improve humanized immune system mouse models was held in Bethesda, Maryland. The four contractors reported progress on their projects to develop, optimize, and test the ability of non-fetal human tissues (cord blood hematopoietic stem cells, neonatal tissue) or porcine thymus tissue transplanted into mice to ensure reproducible immune reconstitution and maintenance in blood, lymphoid, and non-lymphoid tissues. Training sessions to share knowledge and techniques for engraftment and characterization of humanized mouse models developed under this initiative are being planned and will be hosted by each contractor.
NIAID’s Collaborative Influenza Vaccine Innovation Centers (CIVICs). On July 25 to 27, 2022, The CIVICs Annual Meeting was held in Bethesda, Maryland with both virtual and in-person attendees. The CIVICs network, comprised of three Vaccine Innovation Centers, a GMP Manufacturing Core, and two Clinical Trial Cores, is focused on design and testing of novel universal and improved seasonal influenza vaccines candidates. The meeting focused on progress during the first 3 years of the program, including vaccine design strategies, preclinical data associated with candidates that have entered or will soon enter the GMP manufacturing pipeline, and coordination of plans for several Phase I clinical trials under the CIVICs program. Information and news about CIVICs can be found at https://www.niaidcivics.org.
Cellular, Tissue, and Gene Therapies Advisory Committee to The Food and Drug Administration (FDA). On June 29 and 30, 2022, the FDA convened panel members, including Hugh Auchincloss, M.D., NIAID Principal Deputy Director, of the Cellular, Tissue, and Gene Therapies Advisory Committee for insight and opinions regarding clinical xenotransplantation. The FDA, xenotransplantation product developers, and other stakeholders engaged in formal presentations and discussions to gain insights and perspectives regarding development of xenotransplant products to ensure safety and efficacy of these products. The meeting focused on human cells that have had ex vivo contact with animal cells and on the transplantation of porcine organs into human subjects and requirements for the potential future conduct of clinical trials. Formal FDA guidance and recommendations are forthcoming.
Autoimmunity and Mucosal Immunology Branch
Autoimmunity Centers of Excellence Plenary Meeting. On May 19 and 20, 2022, NIAID and the Autoimmunity Centers of Excellence (ACE) held a virtual meeting with investigators from all 10 Centers presenting their findings and plans (Chicago, Mass General Hospital, Weill-Cornell, Emory, Oklahoma Medical Research Foundation, Feinstein Medical Research Institute, Pennsylvania, Michigan). The group previously updated and posted their public progress report on their broad, coherent agenda (autoimmunitycenters.org). The status of ongoing clinical projects was updated (ALE10, ALE11, APG01), including a trial of COVID-19 vaccination (ACV01), and plans were made for additional mechanistic studies using samples from recently concluded trials (ARA08, ALE09).
Radiation and Nuclear Countermeasures Program (RNCP)
Annual U01 Radiation-Induced Vascular Injury Meeting. On May 24, 2022, the NIAID/RNCP conducted the fifth and final annual U01 investigator meeting for the funded RFA on “Elucidation of Mechanisms of Radiation-Induced Endovascular Injury and Development of Treatments/Mitigators for Radiation-Induced Endothelial Cell and Vascular Dysfunction.” The objective of the meeting was to provide an update on the progress made in the respective U01 grants over the past year, and to highlight the overall success of the 5-year program. Through collaborative funding, strong ties were made between researchers in the portfolio, resulting in the generation of new ideas and data for future solicitations. The meeting involved project PIs, NIAID and other IC staff, representatives from regulatory agencies, and other parts of government that have overlapping scientific interest.
2022 Radiation-Induced Multi-Organ Injury Workshop. On June 7 and 8, 2022, a virtual workshop was held to better understand the etiology of multiple organ injury and the early effects of radiation that contribute to this dysfunction. This workshop brought together researchers in radiation biology and related medical fields to discuss their latest research into multi-organ injury and to consider the mechanisms driving injury. The workshop also highlighted currently available animal models and their use in the development of treatments as well as examples of medical countermeasures that could work in various organ systems. The workshop was well attended (>170 attendees) and a meeting report will be published in a peer-reviewed journal.
2022 Gastrointestinal Acute Radiation Syndrome (GI-ARS) Workshop: Mechanisms, Models, Markers, and Medical Countermeasures. On August 29 and 30, 2022, a hybrid in-person/virtual workshop brought together scientists from academia, industry, and government to assess the state of the science addressing GI-ARS. Program staff from NIAID, FDA, and BARDA planned the workshop, which included speaker sessions on clinical manifestations of GI injury and GI-ARS, animal models, mechanisms and biomarkers of GI-ARS, and approaches currently in development. In addition, a session dedicated to regulatory issues was included with speakers from FDA. A meeting report will be published in a peer-reviewed journal in 2023.
FY 2024 Research Concept Clearances Presented to Division Advisory Council
The subcommittee endorsed and unanimously approved the following five Research Concept Clearances:
Consortium for Food Allergy Research, Clinical Research Units (U01, Clinical Trial Optional): The Consortium for Food Allergy Research (CoFAR) will conduct clinical research in the areas of prevention and treatment of food-induced allergic conditions including IgE-mediated food allergy, eosinophilic esophagitis (EoE), food protein induced enterocolitis syndrome (FPIES), and alpha-gal syndrome (AGS).
Consortium for Food Allergy Research, Clinical Research, CoFAR Leadership Center (UM1, Clinical Trial Required): The Consortium for Food Allergy Research (CoFAR) will conduct clinical research in the areas of prevention and treatment of food allergy and its underlying mechanisms.
Vaccine Adjuvant Discovery Program: The objectives of the program are 1) discovery, 2) lead optimization and characterization, and 3) early-stage development of novel vaccine adjuvant candidates.
Development of Radiation/Nuclear Medical Countermeasures (MCM) and Biodosimetry Devices: This broad agency announcement will accelerate advanced research and development of candidate medical countermeasures or biodosimetry approaches for use during a radiation public health emergency. Funding will be provided to support efforts needed to advance products toward an investigational new drug application or investigational use only application to the FDA. The focus will be on MCMs to treat acute radiation syndrome (ARS), and/or delayed effects of acute radiation exposure (DEARE), or biodosimetry tools for use during a radiological or nuclear incident.
Sex Differences in Radiation/Nuclear Research Models: Underlying Pathways, Biomarkers of Inquiry, and Medical Countermeasures Responses (U01, Clinical Trial Not Allowed): This request for applications will enable early-stage research to better understand underlying causes of radiation-associated sex differences, thereby improving medical countermeasure development and biomarker identification in both sexes.
V. Report of the Microbiology and Infectious Diseases Subcommittee–Emily Erbelding, M.D., M.P.H., Director, DMID
Dr. Emily Erbelding, Director of the Division of Microbiology and Infectious Diseases (DMID), chaired the NIAID Microbiology and Infectious Diseases Council Subcommittee meeting on September 12, 2022. She provided a DMID personnel update, recognizing new staff appointments made in the Division since the last Council meeting, including Kamal Velmuragan and Annie Gersh in the Office of Biodefense, Research Resources and Translational Research (OBRRTR); Joy Beeler-Knights, Iman Barton, and Liz Akoth in the Office of Clinical Research Affairs (OCRA); Andrea Lerner in the Office of Clinical Research Resources; and the appointment of Jae Arega as the Director of the Office of Regulatory Affairs. She also noted that Dr. Beeler-Knights was appointed Deputy Director of OCRA.
Following staff introductions, Dr. Erbelding provided a report on recent DMID activities of note:
- Drug company Takeda recently secured approval by the Indonesia National Agency for Drug and Food Control for the company’s dengue vaccine, QDENGA® (Dengue Tetravalent Vaccine [Live, Attenuated]) (TAK-003) for the prevention of dengue disease caused by any serotype in individuals 6 years to 45 years of age. Dr. Erbelding noted that DMID provided extensive preclinical and early clinical development of the vaccine through grants, contracts, and support through preclinical service programs.
- NIAID senior staff published “Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness,” which outlines prototype pathogen strategies for vaccine and monoclonal antibody development, an important component of pandemic preparedness.
Guest Speaker: Urgent Priorities in Sexually Transmitted Infections in the United States, 2022: Jeanne Marrazzo, M.D., Professor of Medicine and Director of the Division of Infectious Diseases, University of Alabama at Birmingham, provided an overview of the U.S. landscape of sexually transmitted infections (STIs) and discussed why they are an urgent priority. In particular, she focused on syphilis, gonorrhea, and genital herpes, summarizing current surveillance data, the burden of disease, and NIH investments in these research areas. She also shared her views on future opportunities and priorities, noting that good point-of-care diagnostic tests that can help reduce the use of syndromic management are essential to stem the relentless STI epidemic.
FY 2024 Concepts Presented for Clearance
The following concepts were presented to the Subcommittee. All concepts were approved.
Sexually Transmitted Infections (STI) Cooperative Research Centers (CRC): Vaccine Development – This concept would support the development of select candidate vaccines through later stages of product development with the goal of creating a candidate ready for Phase I clinical testing. The DMID Subcommittee recognized the importance of the continued development of vaccines for gonorrhea, chlamydia and syphilis through the support of IND-enabling studies and agreed that vaccination is the most effective form of infectious disease prevention. One Subcommittee member inquired as to whether individuals can acquire syphilis multiple times (suggesting that natural immunity is not a component of syphilis) and it was agreed that, yes, this is known to happen. Another Subcommittee member asked whether combination vaccines were of interest. Program acknowledged that combination vaccines would be allowed but noted it is rare for combination or dual indication vaccines to enter into advanced vaccine development.
Advancing Development of Diagnostics for Congenital and Acquired Syphilis – This concept would help move promising technologies through the pipeline towards the development of new diagnostics for syphilis. The DMID Subcommittee recognized the importance of addressing the rise in syphilis rates over the last decade in adults and in newborn children. They agreed that diagnostics were needed for both forms of the disease but especially needed for congenital syphilis to more efficiently determine the disease status between mother and child. The Subcommittee recognized that there is a need for better direct detection of treponemes to complement serologic diagnosis. One Subcommittee member inquired as to whether nucleic acid amplification test (NAAT) technology was sensitive enough to pick up treponeme DNA in blood samples. Program responded that the technology was capable of performing at this level and the purpose of this concept was to further the development of this and other viable technologies into diagnostic products. The Subcommittee members noted the magnitude of this problem and need for better diagnostics to help address it by making the treatment algorithm more efficient, thereby reducing the time to treatment for patients.
Preclinical Models of Infectious Diseases (PCMID) – This concept would support and facilitate therapeutic and vaccine development efforts of the extramural research community by evaluating the efficacy of candidate countermeasures in relevant animal and animal replacement models and by providing reagent resources that require in vivo production. The DMID Subcommittee recognized the value and productivity of the program, which supports countermeasure development for a broad array of infectious diseases. Subcommittee members noted that the program maintains a good mix of focal areas and capably fulfills priority programmatic needs. The Subcommittee was very supportive of the use of the indefinite delivery indefinite quantity (IDIQ) contract mechanism, observing that it permits this contract program to pivot quickly in response to unanticipated events like outbreaks or pandemics, while still maintaining the more complex and time-intensive capabilities like model development and reagent production. The Subcommittee suggested that NIAID conduct regular program reviews to clarify evolving needs and identify valuable new technologies in order to optimize capabilities and ensure that the program continues to ably address programmatic needs.
Genomics Centers for Infectious Diseases – This renewal concept would support hypothesis-driven research in pathogen genomics and related technologies to understand and assess, on a large scale, how genetic diversity of pathogens contributes to infectious disease establishment, severity, transmission, and drug resistance. The program also serves as a resource for the research community through the dissemination of best practices, training and tools related to genomics. The Subcommittee acknowledged that the concept addresses a high-need area and was supportive of the program’s ability to consistently incorporate new and innovative technologies in all areas of genomics. Subcommittee members pointed out the need for investigators to clearly address the rationale for the choice of pathogens to be studied. Because the nature of the program will result in the generation of large amounts of data, the Subcommittee emphasized the importance of consistent sharing of these data and resources to ensure maximum benefit to the scientific community. One Subcommittee member encouraged maximizing collaborative opportunities with investigators from the broader scientific community to further increase the program’s visibility. Overall, the Subcommittee was highly supportive of the renewal of the Genomic Centers for Infections Disease Program.
Therapeutics for eliminating Hepatitis B Virus cccDNA – The objective of this concept is to support the development of novel lead compounds that could eventually be developed for use either alone or in combination with other approaches for a functional cure of chronic hepatitis B virus (HBV). The Subcommittee acknowledged the need for, and timeliness of, this new concept focused on elimination of HBV cccDNA, the key determinant of HBV persistence, and the concomitant development of sensitive and reliable assays to monitor HBV cccDNA. The Subcommittee appreciated the rationale for the proposed two-phase mechanism of funding with milestone-driven considerations to guide transition of selected projects to the second phase.
Development of Medical Countermeasures for Biodefense and Emerging Infectious Diseases - This concept would support the preclinical and early clinical development of candidate vaccines, therapeutics, diagnostics, and platform technologies for NIAID priority biodefense and emerging infectious disease pathogens. The Subcommittee members noted the success of the program to date and were in agreement that the program was important to maintain. The concept fulfills several critical ‘niches’ in medical countermeasure (MCM) development and provides an important translational research opportunity for the research community to facilitate the progression of innovative science into products. One of the Subcommittee members noted that the concept de-risks MCM development for industry, enabling ‘high risk-high reward’ investments, a risk that is difficult for companies to take on themselves. It was also acknowledged that the concept is purposefully broad to cover the development of vaccines, therapeutics and diagnostics and will address unmet needs in biodefense, emerging infectious diseases, and pandemic preparedness and response.
Limited Competition: Resources and Workforce Development for the Regional Biocontainment Laboratories - This concept would provide support to the NIAID Regional Biocontainment Laboratories (RBLs) to enable them to develop and maintain the resources, staff, and facilities necessary to address biodefense agents, emerging infectious diseases and pandemic preparedness research needs. One of the Subcommittee members noted that the RBLs are an invaluable resource that needs continued maintenance and support, especially in the face of emerging disease threats and potential pandemics. Another Subcommittee member suggested that DMID think prospectively about how these facilities can be positioned to more rapidly and efficiently respond in the face of an emergency, which was part of the original intent of the RBL awards. It was also suggested that DMID provide oversight regarding how resources are used in these labs. Program staff noted that this effort will likely be supported using a cooperative agreement mechanism, which will enable close interactions between program staff and the RBL investigators.
VI. Joint Meeting of the AIDS Subcommittee and AIDS Research Advisory Committee (ARAC)–Carl Dieffenbach, Ph.D., Director, DAIDS
Dr. Freedberg welcomed everyone and the ARAC members unanimously approved the minutes of the June 6, 2022 meeting. He noted that this will be the final meeting with Dr. Anthony Fauci as head of NIAID; he thanked and praised his unparalleled leadership and substantial scientific contributions during that time.
Tribute statement read by Dr. Freedberg: “On behalf of the AIDS Research Advisory Committee (ARAC) I want to take a moment to reflect, as we open the September 2022 meeting, the last ARAC meeting under the NIAID leadership of Dr. Anthony Fauci. As you all know, Dr. Fauci has led NIAID since 1984, and it is impossible to capture the enormity of his contributions. His extraordinary leadership of NIAID, and through it the Division of AIDS, has been unparalleled. His ability to see the world, and make it better, has been astonishing- from the most fundamental scientific questions, to the most difficult clinical problems of our lifetimes, to the many public health challenges the world has faced over the past 40 years, in HIV and so many infectious and other diseases. These efforts have had profound and lifesaving effects, on individuals, communities, and the entire world. We thank him, on behalf of people everywhere, and we look forward to what will no doubt be continued extraordinary accomplishments as he opens a new chapter. Thank you Dr. Anthony (‘Tony’) Fauci.”
Carl Dieffenbach, Ph.D.
Dr. Dieffenbach also thanked Dr. Fauci for his extraordinary leadership.
The recent passing of Neal Nathanson was acknowledged. CAPT Robyn Neblett Fanfair M.D., M.P.H., was introduced as an ex-officio member serving as the Acting Division Director, Division of HIV Prevention at the National Center for HIV, Viral Hepatitis, STD, & TB Prevention at the CDC.
Key points for FY 2023:
- There is a House mark of a 5.1 percent increase, and a Senate mark of about a 2 percent increase.
- An exact figure has not yet been determined. Importantly, the numbers exclude the OAR transfers so the final budget for the Division of AIDS will be formed after the appropriations bill has formally been passed.
NIAID FY 2023 Interim Financial Management Plan
- The R01 payline percentiles were 10 percent for established PIs and 14 percent for new PIs.
- No adjustments to noncompeting and competing grants.
- Competing research initiatives tentatively set forth with a cut up to 20 percent.
- Estimated success rates: 18 to 22 percent.
Scientific and Programmatic Updates
Diversity, Equity, Inclusion and Accessibility (DEIA) Highlights
Center for AIDS Research (CFAR) Initiatives - Ongoing CFAR activities were highlighted and included:
- CFAR Adelante program
- CFAR Diversity, Equity, and Inclusion Pipeline Initiative (CDEIPI)
- EHE topic: “Equity-focused Approaches to Reduce HIV-related Health Disparities” – 2-year supplement awards to CFARs and NIMH ARCs
Re-issued R21 PAR: Transgender People: Immunity, Prevention, and Treatment of HIV and STIs
Minority HIV Investigator Mentoring Program and Hakim International Investigator Mentoring Programs administered by the ACTG Underrepresented Populations Committee
HIV/AIDS Network Coordination (HANC) Legacy Project developed the Representative Studies Rubric (RSR) to ensure diverse representation of participants in our clinical research.
- The RSR consists of a 12-item questionnaire that examines study protocols for their representation of people based on age, ethnicity, gender, injection drug use, pregnancy, race, and sex assigned at birth.
- A retrospective study of 47 network studies was done in 2021, a working group has been formed and the RSR is now being piloted at each network during protocol development.
Update on COVID Studies
- Long-term safety and efficacy follow-ups for ACTIV-2 trial.
- ACTIV-2d (looking at the Shionogi S-217622 protease inhibitor) is enrolling in the United States.
- All USG supported phase three COVID 19 vaccine studies are enrolled and in safety follow-up or at a point now where they are nearly completed.
- The Moderna mRNA 1273 (SPIKEVAX) was approved as a two-dose primary series and is licensed for 18 and over and they received EUA approval at a lower dose for six months and up.
- It is expected that within the next couple of weeks, the FDA or the CDC will make recommendations on extending the age for the bivalent boost.
- Sanofi’s pre-EUA package has been submitted for its primary series indication.
CHAVD and IPCAVD Teams at the Duke Human Vaccine Institute Groups Collaborations to Provide Duke Protocols and Advice for mRNA-LNP Manufacture
This group has developed significant protocols for development of an mRNA-LNP type vaccine and how to manufacture it. This approach has been shared with a number of collaborators that includes the NIAID Vaccine Research Center, with a goal of making mRNA technology a true platform for vaccine research.
NIAID Research Priorities for Monkeypox
NIAID has five pillars of research priorities:
- Addressing gaps in basic virology and immunology
- Understanding transmission
- Fostering development of new diagnostics and assays
- Evaluating existing and exploring new treatment strategies
- Optimizing and advancing the vaccine regimens
Study of Tecovirimat for Human Monkeypox Virus (STOMP) Trial (A5418)
This recently opened trial is a randomized placebo controlled double-blinded trial that seeks to evaluate the safety and efficacy of Tecovirimat for the treatment of human monkeypox disease.
It was noted that this is a 2:1 randomization that will stack the deck in favor of getting people treated. Time to resolution is being looked at where the endpoint is clinical resolution. This is when all skin lesions are scabbed over or desquamated, and all visible mucosal lesions have healed. Importantly, this is an open label study enrolling pregnant people and children, looking at fractional dosing that is needed to treat children.
Q: RE: the representative studies rubric (RSR), there’s unintended exclusion occurring so what's the plan for lessons learned here and getting these out to everybody so that we can all make sure that we don't make the same mistakes?
A: That's exactly what's going on right now. HANC and others are piloting this within protocol development within every network so that we are more precise in our language as we go forward. There's a sense that that's where we'll start and then get it out to other investigators that will need this as well. It is actively going on; thanks to HANC and the Legacy team.
Q: Just to confirm you did say every network, under DAIDS, will be involved with developing or adhering to or reassessing their accessibility and inclusion practices.
A: Yes. ACTG is doing it to start, and our goal is to have this move to every network.
Comm: The CFAR CDEIPI programs have been amazing, and I really wanted to thank you all for supporting it because CFARs were never able to support people from undergraduate or master level programs.
Q: If disadvantaged students are from socioeconomic disadvantages, beyond racial ethnic minority status, this fits into our mission in the CFAR CDEIPI programs because when you get to a “K” the socioeconomic disadvantage doesn't count as much as being in the URM category.
A: At the NIH level we categorize that as a disadvantaged group as well, and I think we will continue to do so.
Comm: I think it's great the third arm mentioned in A5418 for children and pregnant people to get that information from the very beginning. That's a major step forward with the trial.
NIH Office of AIDS Research (OAR) Update: Women’s Health and HIV Research Activities in FY 2022
Leslie Marshall, Ph.D.
On behalf of the OAR, Dr. Leslie Marshall presented topics on Women's Health and HIV Research Activities at NIH.
Women and HIV Globally in 2021
Key data on the prevalence and incidence on this topic for 2021 was presented including:
- 54 percent (~20 million) of all people living with HIV were women and 20 percent of transgender women were living with HIV.
- 49 percent of new HIV infections were in women and transgender women have 14-times higher risk of acquiring HIV.
Reaching Ending the HIV Epidemic (EHE) Goals
In the United States, CDC reports that about 18 percent of new HIV infections in 2019 were among women and approximately 23 percent of all persons with HIV in the U.S. are women.
Progression towards epidemic control targets is better among women overall across the cascade but are considerably suboptimal for retention of care and viral suppression, making transmission inevitable.
Important Areas of Research for HIV/AIDS and Women
As HIV affects women and girls differently across their lifespan, the NIH HIV Research Agenda for Women should be tailored appropriately. Key focal areas include:
- HIV during pregnancy and lactation
- Early childhood consequences of HIV exposure
- HIV and menopause
- Implementation research
- Gender-affirming and trauma-informed HIV care for transgender people
- The role of sex and gender and efficacy of HIV interventions, including prevention, treatment, and cure
Other topics briefly discussed:
- NIH OAR active engagements with HIV/AIDS research community including the Inter-CFAR women and HIV symposium and the 2022 Annual Meeting of Women’s Research Initiative on HIV/AIDS
The NIH vision for women's health includes three principles:
- Integration of sex and gender into biomedical research
- Every woman receiving evidence-based care
- Women in science careers reaching their full potential
The structure of NIH enables maximum impact of HIV research for women and girls. The NIH OAR and the Office of Research on Women's Health sit within the Office of the Director and these offices collaborate across other NIH Institutes and Centers and Offices (ICOs) to ensure synergy and advancement of research topics of interest for women living with and at risk for HIV.
Women's Health Research at the NIH: NIH OAR Activities in FY 2022
NIH OAR is playing key roles in responding to Congress’ 2021 request for an update on and further investment in NIH efforts related to women's health research with a specific emphasis on rising maternal morbidity and mortality rates and rising rates of chronic debilitating conditions in women.
- In 2019, NIH had initiated maternal morbidity and mortality efforts across the organization through formation of an advisory cabinet comprised of senior NIH leaders and a maternal mortality task force (MMTF) comprised of key subject matter experts from all the ICOs.
- The Implementing a Maternal health and Pregnancy Outcomes Vision for Everyone (IMPROVE) initiative was the first deliverable from the MMTF and received $30 million from Congress.
Women in the Biomedical Workforce
- COVID-19 has exposed and exacerbated the barriers that women have been experiencing for decades in the STEM fields and are more likely to exit the workforce because of pandemic household responsibilities.
- NIH is working to remove barriers for women in research careers by increasing funding for research for women with HIV/AIDS, taking into consideration childcare costs for NRSA fellows, increasing diversity in the female workforce by different mechanisms, and providing supplements for COVID-19 research disruptions.
- The Women's Health Research Biennial Report for Fiscal Years 2019 through 2020, a new publication from women leaders on establishing inclusive excellence at NIH were briefly discussed.
The NIH commitment to inclusivity and diversity in the NIH/AIDS research workforce was emphasized and highlighted a commitment to the UNITE Initiative and proactive implementation of DEIA principles amongst other strategies.
Q: Women and girls potentially at risk for HIV may not recognize or be aware of their risk and not fully appreciate that it even exists. This makes it more difficult for them to be proactive and pursue potential remedies or options in our prevention toolbox. Any thoughts about work being done in that area about raising awareness and helping women and girls recognize their risks?
A1: There's a lot of effort being put into this area, especially with the advent of new innovative long-acting prevention. Organizations developing these technologies are committing to equitable access and to incorporating that into the practice.
A2: With the 27 Institutes and Centers at NIH, a lot of the behavioral and social science work is done in partnership with NIAID by the NIMH Division of AIDS Research led by Dianne Rausch; they are co-housed within our organization and it is this important intersection between, not just availability of the biomedical intervention, but also helping to meet people where they live so they can understand their risk, and also understand the stigma they feel and what's needed to help them develop the cultural competency to access these relatively complicated biomedical interventions.
Concepts – Approval Requested
DAIDS Basic Sciences Program
Opportunities for HIV Cure Strategies at the Time of ART Initiation
Brigitte Sanders DVM, Ph.D. and Leia Novak, Ph.D.
The objective of this grant initiative is to identify new opportunities for cure strategies near the time of ART initiation in cellular or animal models or as a replacement for conventional ART, with the ultimate goal of achieving a sustained ART-free HIV remission.
Current HIV cure approaches focus almost exclusively on strategies after complete ART suppression. Recent literature reports suggest that most of the viral reservoir becomes stabilized at the start of ART and some approaches in the absence of ART have resulted in sustained remission in NHP. The question sought to be answered is are any opportunities to intervene before complete ART suppression or after an analytical treatment interruption when HIV antigen is actively stimulating the immune response to improve the outcome of an HIV cure? Current timing and outcomes of conventional ART curative strategies were presented as a graph with the proposed timepoint of the new intervention.
Recently published longitudinal levels of plasma HIV RNA after ART initiation showed a biphasic decay and that ongoing virus reduction occurs mostly in the first 3 months of the infection. Between 3 and 6 months, HIV production declines more slowly after which time point it becomes undetectable. Therefore, starting interventions concomitantly with ART may accelerate the time to full suppression of viremia and may reduce the size of the latent reservoir.
Relevant published reports were summarized which showed: 1) the latent viral reservoir is already largely established at the time of ART initiation; 2) immunotherapy during acute SHIV infection confers long-term suppression of viremia in the absence of ART; 3) AAV delivery of anti-HIV monoclonal antibodies can drive long-term virologic suppression without ART; and 4) results from the eCLEAR study which showed people treated with romidepsin during ART initiation had an increased proportion of p24+ CD4 cells, confirming latency reversal.
The scope of this study covered basic research to map HIV/SIV seeding, analyzing HIV reservoir dynamics and comparing reservoir or immunologic changes in response to strategies delivered at different timepoints. Applied interventions should identify experimental approaches in cell or animal models and identify short-term strategies in preclinical models instead of or in combination with ART.
Reviewers’ comments for the concept were summarized and the responses were discussed.
Pulmonary Outcomes and Sequelae after Treatment for TB (POST-TB)
Robin Huebner, Ph.D., MPH
The purpose of this new grant initiative is to support epidemiologic and observational research to better characterize and understand adverse outcomes and morbidities associated with tuberculosis (TB) disease post-treatment in HIV-infected individuals.
Of the world's population, 23 percent is infected with M. tuberculosis and there are more than nine million new cases annually, of which 1.1 million are under the age of 15. Despite cure, up to 50 percent of patients have persistent pulmonary dysfunction at the time of treatment completion. Importantly, potentially 1.75 million persons with HIV may have persistent lung damage from TB and therefore is not a minor problem.
Scientific issues to be addressed by this initiative include: 1) TB disease and its aftermath are the leading cause of death in people living with HIV. Individuals previously infected with TB are more likely to die within the first few years after treatment even if considered cured; 2) Lung function and immune responses post-treatment in adults and children with HIV. Little is known about the prevalence and clinical manifestation or if there are differences by HIV status and treatment; and 3) Are there structural barriers to effective post-TB lung health?
Little is known about the long-term sequelae of TB disease post-treatment and less is known about how HIV impacts that, the interest is in HIV and HIV treatments, immunologic factors, biomarkers, and also alcohol and tobacco use, nutritional status, environmental exposures. This initiative is aimed at better understanding the impact of HIV ART, the host immune response, and other strategies to reduce the burden of long-term sequelae following the treatment for TB. Requirements for responsive applications included enrollment of patients from existing cohorts of TB patients and those for non-responsive applications included evaluation of individual TB drugs or drug regimens for lung toxicity.
Reviewers’ comments for the concept were summarized and the responses were discussed.
Q: Is the pediatric component dependent on getting NICHD funding and partnership?
A: I don't believe so necessarily because I have been working on this with our own pediatric group and they're very interested as well as with the TB team. If we get a good pediatric application, we would not rely on NICHD funding if it was HIV-focused.
DAIDS Vaccine Research Program
Synthetic Nucleic Acid Platforms for HIV-1 (SNAP-H)
Angela Malaspina, Ph.D.
The objective of this new grant initiative is to advance nucleic acid-based platforms for the rapid development and testing of prophylactic and therapeutic vaccines and for the delivery of broadly neutralizing antibodies (bNAbs) and bNAb derivatives for HIV prevention, treatment, and cure. Key features of the program include an R61/R33 two-phase grant mechanism which incorporates milestones, and it encourages translational partnerships between academia, industry, and government.
The COVID-19 pandemic established that synthetic nucleic acid approaches (RNA/DNA) can speed up product development and testing. Objectives include whether nucleic acid approaches can be used for different types of HIV immunogens, elicit stronger broader and longer-lasting HIV specific immune responses, and support the delivery of multiple bNAbs or bNAb derivatives for the prevention, treatment and cure of HIV. The challenges include HIV sequence diversity amongst others. However, there are advantages of RNA/DNA platforms such as their safety, scalability, and versatility.
Relationships to other awards and programs and the NIAID/DAIDS RNA/DNA pipeline for 2021-2023 were summarized. Several examples were presented and included to define events after immunization to optimize responses and evaluate strategies for stabilization of immunogenic epitopes.
Reviewers’ comments for this concept were summarized and responses to their questions were addressed.
Q: Will you do both active and passive immunization in this mechanism?
A: Yes. At a workshop in May about the development of broadly neutralizing antibodies, there was a session on the platform development and delivery where there was a knowledge gap. So, we thought this was an opportunity here to add this point because it really would allow more global access to this intervention.
Q: I guess it's too late to change the title to include that aspect, but I guess there may be a lot of people who won't know about it?
A: This is actually very vague in our title, but we will consider that.
Rational Systemic Characterization and Selection of Adjuvants for HIV Vaccine Candidates (R-CASA)
Milton Maciel, Jr. PharmD, Ph.D.
The objective of this new contract initiative is to facilitate the development of optimized, HIV immunogen adjuvant combinations to include functionality, durability, and magnitude of HIV vaccine-induced immune responses and enable rational selection of adjuvanted HIV vaccine formulations based on desired immunological profile.
In 2018, the Strategic Plan for Research in Vaccine Adjuvants defined three major areas that needed to be addressed: (i) Fundamental immunology and adjuvant discovery, (ii) Adjuvant development and preclinical evaluation and (iii) Clinical evaluation of adjuvanted vaccines. A summary of 2 decades of NIAID adjuvant research efforts was presented which included DAIDS collaborations with DAIT. However, DAIDS currently has no dedicated funding mechanism specifically focused on the preclinical development of HIV immunogen and adjuvant formulations. Some conclusions of the recent DAIDS workshop entitled Optimizing Immunogenicity of HIV Vaccines by Adjuvants was presented and included the unique challenges of the lack of evidence for broad natural protection and consequently no defined correlates of immunity, the lack of a human challenge model and the need for more models to evaluate therapies and vaccines. Current clinical understanding indicates that an HIV vaccine will have to properly mobilize an innate immune system to activate an adaptive immune response. This will have to be multimodal and involve all arms of the immune system: neutralizing antibodies and T-cell response. Investigation of the immunogens and adjuvants formulations, new adjuvants and combinations of adjuvants improve the immunization strategies and immunogenicity platforms which are pivotal to support the development of the HIV vaccine.
The R-CASA initiative intends to support biochemical and immunological systematic characterization in the screening of HIV immunogens and adjuvant formulations and establish ‘go/no-go’ criteria with standardized methodologies which will generate important knowledge to further the development of an HIV vaccine.
Challenges to expanding the investigation of new adjuvants for HIV vaccine formulations include that immunogen developers usually choose adjuvants based on convenience and so very few new adjuvants are clinically tested and/or are in clinical trials. Also, adjuvant developers are usually reluctant to share their products (IP issues) and have aversion to undermining forthcoming licensure for pre-conceived pipeline. Ways to engage collaboration between HIV immunogen and adjuvant developers were noted. Examples of why the formulation of the immunogen plus adjuvant should not physically damage the immunogen was shown. The HVTN 137 Phase 1 clinical trial that looked at different doses of the TLR agonist adjuvant was briefly discussed.
Applications for the rational systematic characterizations for selected adjuvants for HIV vaccine result candidates should propose a series of HIV immunogen and adjuvants, create a matrix for assessment of formulations, as well as biochemical and co-methodologies by which those formulations will be systematically characterized and screened.
Reviewers for this concept were supportive. Their comments and suggestions were addressed.
Q: It seems like a rather difficult chess game as you don't really know where to start with the immunogen or the adjuvant and maybe there's some adjuvants are better for different immunogens? What are your thoughts on that?
A: Our rationale to promote the initiative that way is to create this matrix so we can in fact select exactly what you were asking about. What combines better with what. So, we started with this well-accepted rationale that each immunogen and adjuvant is a unique marriage. And we can expand observations from one antigen to the next, right. We have this general idea that if you work with one antigen, it could just move on and plug in with the same adjuvant. We think that we need to be prepared before we move forward with formulations to make sure that each one of these matches – this adjuvant with that immunogen – can in fact work, and we are proposing this preclinical platform to assess that.
Q: I’m unclear about the concepts for what you look at and what you do. Do things originate from whoever gets this contract, or are there mechanisms for outside people with ideas to filter into it?
A: We provide the parameters, and they tell us how they're going to get the work done. We are planning for a Broad Agency Announcement (BAA) so we will receive the proposal. The government has some flexibility in deciding what to accept. We can accept part of the proposal and we can even propose specific combinations of immunogens and adjuvants that we want to be part of the comparison.
Innovation for HIV Vaccine Discovery (IHVD)
Jon Warren, Ph.D.
The objective of this reissue grant initiative is to stimulate novel, high-risk/high-impact, early discovery research that may have a significant impact on the design and development of successful strategies for an effective HIV vaccine. There continues to be a need to vigorously support early discovery and truly innovative HIV vaccine research, and to fully leverage the accelerated significance of vaccine research catalyzed by the COVID-19 pandemic. As a noteworthy change from prior IHVD FOAs, the primary focus of this initiative will be to support novel, exploratory not-as-yet proposed vaccine discovery research for designing an effective HIV vaccine, though secondarily it may also consider support for worthy novel basic vaccine discovery research that has not been fully exploited.
To ensure as the primary aim that novel exploratory research applications are evaluated on their ideas, this IHVD PAR will state that: 1) because R01 applications often can be much less competitive in the risk-averse context of conventional peer review, limited or the absence of preliminary data in the application should not negatively impact the score (this is significantly different from most R01 projects); and 2) inclusion of Go/No-Go milestones with clear metrics are to be achieved by the Year 2 Progress Report and will be evaluated by Program before additional funding is provided.
Research areas of interest include but are not limited to: novel vaccine approaches to elicit durable cellular responses and/or humoral protective immunity against HIV, SHIV, and/or SIV; novel strategies to direct protective adaptive and/or innate immune responses to relevant anatomical sites (e.g., vaginal and/or rectal mucosa, and secondary lymphoid tissues); exploring mechanisms of vaccine induced/imprinted innate immune responses that can be recalled in response to subsequent vaccination or infection; and exploring the utility of novel platforms for immunogen delivery.
Non-responsive research areas include product development or human clinical trials. A summary was provided of the six previous IHVD initiatives since 2012.
The preliminary reviewers of this concept were strongly supportive, and their suggestions were summarized.
Q: How do you come up with the years to fund? Is it what's available or it's been successful in the past? I can imagine if you come up with something extremely novel, it may take more time to develop [within the four-year grant].
A: Currently, applications go to peer review and get scored and that's a typical R01 and it can be funded through the payline funds. I should have mentioned, if nonhuman primates or humanized mouse models are used, the investigators will have up to a $150,000 or thereabouts per year to support those activities. At one point in time this grant mechanism was a biphasic R21/R33, which was 5 years of support for the R33 post-transition, then it became an IHVD of 5 years with no transition, and then we went back to the R01 this time with 4 years and the amounts of money that were used to fund each of those different iterations of this program varied, but it has been fairly consistent over time. We are asking for $2M for the first year of this new 3-year PAR beginning in fiscal year 2024.
Comm/Q: It strikes me that part of this starts to intersect a little bit with the SNAP-H that we heard about earlier in terms of some of the mRNA platforms and I imagine that you'll handle that, is something innovative or not in these conversations that you want to have? Is there a cross-reference for more products or approaches further along the developmental pathway and might consider this concept as well? Have you thought along those lines?
A: In a sense, Angela's SNAP-H initiative is in part a further highly important developmental phase of the Weissman/Karikó platform for mRNA with the nanoparticles of which there were 14 NIH-supported patents submitted by Drew Weissman and his group at Penn over more than a decade and well before Moderna was even in this field. Nine of those patents cite their innovation grant in 2016. This is not in a vacuum; these innovation grants go somewhere, but most of them fail. In terms of SNAP-H and how it will communicate with the innovation grant program, which we hope also include further development of nucleic acid-based vaccines, not just RNA but DNA. We'll have to see where that goes but we won't turn down further developmental aspects. What Drew Weissman did over many years, for the innovation grant that was awarded in 2016, they received two no-cost extensions and its final report I received last month. even though it was funded 6 years ago, and he had also done all kinds of developmental work, especially the modifications to basically make the mRNA silent to the innate system. At a meeting, in 2014, one of the things Dr. Weissman was talking about was showing that lipid-nanoparticles by themselves could be adjuvants independent of the mRNA. So that work has been taken on by other grant mechanisms that expanded extensively. We're certainly going to communicate that if the SNAP-H gets some traction, we hope to certainly interact going forward.
Comm/Q: Innovation being key, novel being key, my question is it would be really nice if the different programs could talk and help the PIs determine which FOA is more appropriate for their innovative proposal because there is actually quite a nice theme that's emerging here between them.
A: Maybe preliminary data is the key. One of the things discussed in the preliminary call with the reviewers was the degree of preliminary data or, this idea that those kinds of data are not necessarily needed for an application for this IHVD. And in my experience, all these grants come in with some preliminary data and sometimes it's relegated to other disease systems, some using that approach that they want to apply to HIV. These are reviewed as a group and the SRO or the study section chair is careful to remind the reviewers that the preliminary data don't have to be necessarily as rigorous as in the typical R01.
Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) Program
Sujata Vijh, Ph.D.
The Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) is a longstanding program that was initiated in 1998 and has evolved over the years to its current state. This is a request for approval of a reissue of this U19 cooperative agreement which requires significant oversight and involvement by program. The purpose of this reissue is to facilitate translation of advanced HIV vaccine candidates from preclinical studies all the way through cGMP manufacturing regulatory filing up to the point of clinical testing. Clinical trials will not be supported.
The objectives of the program include translation of vaccine platforms that elicit primarily broadly neutralizing antibodies; known selection of mature HIV vaccine candidates by a multidisciplinary group of experts, such as immunologists, vaccinologists, structural biologists, animal modelers, adjuvant biologists, and others. Given the reluctance of industry to take financial risks to invest in HIV vaccine development, the main objective of the IPCAVD is to foster partnerships within academia that brings ideas and innovation to the table.
An overview of the IPCAVD programs covering the translational research and supported activities was presented. This includes the requirement for multidisciplinary teams of experts from all stakeholders, including DAIDS, industry, and the grantee organization. The importance of the IPCAVD is that it has fostered over the years several successful and unique partnerships between academia, industry, and DAIDS that would not have occurred without this mechanism. An overview of the achievements of the IPCAVD Programs in the last 15 years of the 24 years it has been in existence was presented.
The scope of this initiative was discussed and covered the following areas of interest: HIV immunogens designed to elicit bNAbs alone or in combination with the innate and or adaptive immune responses; stabilized HIV envelope protein immunogens designed to minimize the response to off-target epitopes; proof of concepts with novel immunogens/platforms; and platforms that offer advantages of dose sparing or accelerated manufacturing processes. For preclinical animal models, studies in nonhuman primates (NHP) limited to immunogenicity studies are encouraged. Efficacy and challenge studies in NHP are not a priority area for support through the IPCAVD.
Some nonresponsive areas include studies proposing gp120 monomer immunogens and applications proposing cGMP manufacture of only adjuvants.
Both preliminary reviewers of this initiative were supportive. Their comments were discussed and addressed.
Q: I understand the resistance to having NHP challenge studies, but I guess that information is needed before this will go into a clinical study, is that correct or not correct?
A: I think we have examples of it being translated in some studies. In some studies, they're not translated. So, we need to strike a balance. It's definitely helpful to have an NHP study that can be repeated and then take the product to the clinic but that would be a really long program.
Q: Sometimes we've had historically real difficulties in manufacturing products, and I guess it's related to why you don't want these NHP challenge studies, but have you had to work previously with these groups where the manufacture didn't go quite as planned and is there flexibility there if they need more time or an extension – would it go back to this Council or something like that?
A: It does take a long time for these programs to come through, especially for biologics and proteins. The mRNA and DNAs are a little bit faster, but even then, given the way we function through the government grant mechanism, there are so many issues and challenges that have come up. For example, the grantee could change institutions, there could be some legal implications when they are trying to negotiate contracts or agreements with manufacturers. The COVID pandemic created a tight supply chain issue, and there was lack of materials that were needed. All of these can add delays to the program, so they end up taking longer. They often go into no-cost extensions. Our attempt for this particular announcement round is to try to shorten the timeline so we don't go into seven years of programs and, yes, there are issues in manufacturability. There are a couple programs that did not make it into the manufacturing itself and some of them have ended earlier because the grant ended but we couldn't finish GMP because the product either did not get to the amount that we wanted to the purity as well as the quality or we couldn't get enough material for the clinic.
Comm: We have a pretty robust program for primate evaluation and there are other ways to get that done without it being part of this grant initiative. The point is that we have flexibility. This is focused on manufacturing and getting towards clinic and the NHP work can be done elsewhere.
NIAID Division of Extramural Activities
NIH Medical Scientist Partnership Program
Matthew Fenton, Ph.D.
This new trans-NIH initiative called the NIH Medical Scientist Partnership Program (MSPP) is being considered for concept approval by the ARAC. It is developed in response to the long-recognized need in academia and NIH to really have a concerted effort to grow the highly valuable physician scientist pipeline. This is a group of scientists that really need extra support and extra opportunities for which to enter the biomedical workforce. There are already several existing well-supported and highly functional programs at NIH that support physician scientists, but there's also an opportunity to expand the kind of support that NIH can provide. It was felt there was an opportunity to expand this NIH support beyond just the 53 MSTP universities to include additional medical, dental, and veterinary schools in the United States.
The MSPP is designed to provide an additional pathway to attract support and train physician scientists and especially trainees who are women and underrepresented minorities and will accept applications from students who will be attending schools that both do and do not have existing combined degree programs.
This initiative will support predoctoral candidates interested in pursuing both a clinical degree (e.g., M.D., D.D.S., D.V.M.) and a Ph.D., whether in a formal combined degree program or not, who wish to conduct their dissertation research at an NIH intramural laboratory. NIH intramural funding will support candidates while they are engaged in their doctoral research. The grant will only support the extramural portion of the training in a medical, dental, or veterinary school for a maximum of 4 years. As with other NIH fellowship grant programs, this Program will only cover stipend, tuition and fees based at National Research Service Award support levels. Importantly, a mentor and research project need not be identified at the time of application. This would only need to be finalized at the time of award. Applications will primarily focus on candidates’ qualifications and accomplishments, their research experience, and their commitment to a research career. We anticipate that applicants will come into this program under two different tracks which are outlined below:
Track 1: The students and post-baccalaureate graduates will apply to NIAID for the grant using NIAID as the applicant organization in August when they are applying to a U.S. medical, dental, or veterinary school, either at the beginning of their senior year of college or later if they are applying to a clinical professional school after graduating from college. They will submit a separate application for the Intramural Research Program Graduate Partnership Program (IRP-GPP) in September of that year. Applications will then be peer reviewed in October or November and will receive a second level of review in January by NIAID’s Advisory Council. A letter notifying students they are being considered for funding would be issued immediately after Council, in which we would note the requirement that the student have an intramural mentor selected by the beginning of their clinical graduate school matriculations. The IRP-GPP will then conduct interviews with the candidates in February and make selections in early March. NIAID will inform the appropriate IC, based on the laboratory the trainee has been matched to. Applicants then submit the finalized information about their mentor via just-in-time, and the Notice of Award can be issued. The award will start at the beginning of their first year of medical, dental, or veterinary school. The grant will cover all 4 years of their clinical graduate school training. Upon successful completion of their dissertation research, a type 4 award will be made for completion of their final 2 years of MD/DDS/DVM training. We expect there will be about a 4-year hiatus in which no grant funding will be provided after year 2. During that hiatus, the student will be fully supported by the IRP laboratory where they will conduct their dissertation research.
Track 2: The students will have to be accepted into a U.S. medical, dental, or veterinary school before applying for the grant through their clinical graduate school using their school as the applicant organization. Students will apply in August as they begin their first year of medical, dental, or veterinary school. IRP-GPP applications, grant reviews, Council review, etc., will all occur as with Track 1 students. The only difference is that funding will only cover 3 years of medical, dental, or veterinary school training. One year will be supported prior to Ph.D. training in an IRP laboratory, and upon successful completion of their dissertation research, a type 4 award will then be made to fund the final 2 years of M.D./D.D.S./D.V.M. training. ICs signed onto this program will support those trainees that do their dissertation research within their IC’s IRP laboratories.
NIAID will be the lead Institute and coordinate with the other participating Institutes.
The MSPP will use a completely new fellowship FM1 grant activity code that is based on individual rather than institutional criteria like the T32 and the MSTP Program.
Q: If you admit or give a grant to an MSTP student, what happens to the money? Do you share the cost of that with the institution or does this program take over that cost?
A: First, the MSTP Program is sunsetting its option of allowing students to do their dissertation research at the NIH campus and this program is substituting for that. The way it has worked in the past is that, under the MSTP, the institution receives a T32 grant with a certain number of slots and the funds to support those slots. The student who matriculates gets into a slot and if that -- but again the T32 is housed at NIGMS. So let's say a student who wants to do a microbiology, or immunology dissertation project gets a slot. NIAID would then co-fund that T32 grant to pay for that student through their four years of schooling. Under the MSPP Program, we're just simply paying directly. It's an individual fellowship grant. We're not paying through a T32.
Q: Does this extend to non-medical Ph.D.’s, in pharmacy, dental, and nursing, in a way that the MSTP didn't serve?
A: We definitely will be including medical, dental, and veterinary. We will likely include some of the other clinical doctorates, but one of the questions that came up recently about RNs and whether there would be an RN/Ph.D. opportunity. Because of the type of grant, it will have to be a combined doctoral degree. It wouldn't be a pathway for someone who wanted to do an RN Ph.D. They would have to go through the regular Ph.D. fellowship grant pathway to do that.
Q: Two questions:
(i) In the four criteria for evaluation that you listed, I don't believe that diversity was one of those criteria. Perhaps it was. But for the T32s, that is a criterion for success and for the program, will that be viewed in this program internally as one of the criteria in evaluating applications is the first question.
(ii) I hadn't realized before you presented that there was no research proposal noted. How will applicants and reviewers know where someone might end up or is this really to find committed people who have done research and expect that they will find a good place to go?
A: (i) If you're doing an institutional grant, we can encourage institutions through the FOA to do their best to encourage and support DEIA in their recruitment practices, but we cannot make an award based on race, sex, gender, or any of those criteria. Legally, we're not allowed to do that. By saying that we want this program to encourage schools, HBCUs and MSIs to participate in the program, by opening it up to schools outside of the MSTP Program to reach out to more diverse colleges and universities. We're hoping that we will automatically increase the diversity of the applicant pool by doing that, but we actually can't take race, sex, gender into account in determining funding.
A: (ii) If you think about a student coming into the MSTP Program, they get a slot on a T32. They have no idea what their research project's going to be, who their mentor is going to be, whether it's in the Intramural Program or not. So, this isn't all that different. We will be putting in the FOA a description of the resources that are available through the Intramural Program and I think everybody's aware of the high-quality research that takes place at the NIH campus. But this is going to be very similar to the existing program, since a student on a T32 slot in the MSTP will be identifying a mentor and a research project in the course of usually their first year in medical school.
Q: RE: in terms of specific topic areas. Will there be some attempt to identify particular high-value areas that are needed by the NIH and that are in line with the priorities that will be given preference? I know you mentioned that there may not be a clear path to select the areas of study necessarily, but I am curious about the topic areas that would be prioritized.
A: The ability to do that kind of prioritization is really limited given that we don't require a research project to be proposed in the grant application itself and, as we discussed, at the time these applications are reviewed, at least for the Track 2 students, they won't have a clear answer for where their mentor and home institution will be in the Intramural Program. Chances are they're very likely to know the types of research that they're interested in. Almost all of these students are going to have prior research experience and have very strong ideas at least up front of where they think they might want to work in terms of their science area. But we're not trying to prioritize one area over another. In the case of NIAID, we'll be looking at students that fit all of the mission areas of NIAID and the need for physician scientists is great enough as we want to take every opportunity to be able to train people in this career path as we can. To try to pre-select early based on some prioritization of an Institute's research is not helping us get as many people in the pipeline as we would like.
Public Comments: None
Ballot Voting Outcome:
The voting members of the Committee unanimously approved the seven concepts presented today.
The meeting of the Council adjourned at 4:00 p.m., on Monday, September 12, 2022.
We do hereby certify that, to the best of our knowledge, the foregoing minutes are accurate and complete.
Hugh Auchincloss, M.D.
Chair, National Advisory Allergy and Infectious Diseases Council
Acting Director, National Institute of Allergy
and Infectious Diseases
Kelly Poe, Ph.D.
National Advisory Allergy and Infectious Diseases Council
Acting Director, Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Council will formally consider these minutes at its next meeting; any corrections or notations will be incorporated in the minutes of that meeting.